Changes in Myocardial Blood Flow And Function With Beta Blocker Therapy in Heart Failure: Background: The addition of beta blockers to standard heart failure therapy improves left ventricular ejection fraction (LVEF) and mortality. However, the underlying mechanism for the beneficial effects of beta blockers in heart failure is not well understood. In this study, we examined the effects of 6 months treatment of metoprolol on absolute myocardial blood flow (MBF) and function in patients with ischemic and non-ischemic cardiomyopathy. Methods: Twelve congestive heart failure patients with NYHA class>II; 6 ischemic and 6 non-ischemic, underwent pre- and post-metoprolol N-13 ammonia PET and radionuclide angiography studies. Changes in MBF and function were examined before and after the addition of 6 months of metoprolol to standard heart failure therapy. Absolute MBF (ml/min/g) was computed from the dynamic N-13 ammonia data using a two-compartment model. Results: Mean LVEF increased from 16+8% pre- to 23+11% post-metoprolol (p<0.005). Among patients with ischemic cardiomyopathy, MBF increased in abnormally perfused myocardium from 0.40+0.18 ml/min/g pre- to 0.54+0.18 ml/min/g post-metoprolol (p<0.01), and decreased in normally perfused myocardium from 0.88+0.31 ml/min/g pre- to 0.61+0.15 ml/min/g post-metoprolol (p<0.01). Such favorable redistribution of absolute MBF in ischemic patients persisted after normalizing MBF to rate-pressure product and was associated with improvement in regional LVEF in abnormally perfused myocardium from 23+18% pre- to 27+22% post-metoprolol (p<0.05) but not in normally perfused myocardium (23+20% pre- and 24+19% post-metoprolol, p=NS). In patients with non-ischemic cardiomyopathy, there was improvement in both regional and global LVEF after metoprolol without associated improvement in MBF.Conclusions: Metoptolol increases regional MBF and function in abnormally perfused regions in ischemic patients but its mechanism of action in non-ischemic patients appears different. Perhaps altered substrate utilization such as fatty acid and/or glucose may provide additional insight into the underlying mechanism for the salutary effects of metoprolol in the non-ischemic patients.